The present invention relates to an adsorbent for serum amyloid (hereinafter referred to as "SA") protein from body fluid. Particularly, the present invention relates to an adsorbent for serum amyloid A (hereinafter referred to as "SAA") protein and serum amyloid P (hereinafter referred to as "SAP") protein from body fluid.
There is a disease called amyloidosis attended with serious troubles, for example, insufficiency of organs such as heart and kidney, disturbance of impulse conducting system, progressive dementia, cerebrovascular disease, nerve trouble and so on. Amyloidosis is caused by a deposition of .beta.-fibril-like amyloid on a blood vessel, a certain organ and so on. It is known that there are some types of amyloidosis, i.e. primary amyloidosis, secondary amyloidosis, familial amyloidosis, senile amyloidosis, and so on, and that the composition of proteins causing amyloidosis differs depending on the type of amyloidosis.
Secondary amyloidosis follows diseases such as rheumatoid arthritis, juvenile rheumatoid arthritis, suppurative diseases of the lung and pulmonary tuberculosis. There are exemplified as favourite localization in secondary amyloidosis, kidney, thyroid gland, pancreas, liver, spleen and the like.
In secondary amyloidosis, deposited amyloids are formed from amyloid A (hereinafter referred to as "AA") protein which is a protein having a molecular weight of 8,500 and composing of 76 amino acids.
It becomes clear step by step that there exist a precursor, in patient's body fluid, corresponding to each deposited amyloid in each type of amyloidosis.
It is considered that SAA protein which is one of apolipoproteins of high density lipoproteins (hereinafter referred to as "HDL") is the precursor corresponding to AA protein being the deposited amyloid of the secondary amyloidosis. SAA protein has a molecular weight of about 12,000, and it is thought that the protein is produced in hepatic cell, forms apolipoprotein of HDL in blood, circulates through the body and separated from HDL to be hydrolyzed to form AA protein, and then, the AA protein is deposited in tissues. Also, it is thought that SAA protein exists as an apolipoprotein of HDL.sub.3 which has a high density compared with other HDL, and has a molecular weight of 1.75.times.10.sup.5.
In the 1960's, it was proved that there are two kinds of amyloids by means of investigation with electron microscope. That is, one is an amyloid having a shape of fiber peculiar to amyloids (amyloid fibrils), and the other is a pentagonal rod-like amyloid (P-component, AP).
In every type of amyloidosis except in macula of cerebrum in Alzheimer's disease or presbyophrenia senile dementia, a substance called amyloid P (hereinafter referred to as "AP") protein can be found in the state of combining with a .beta.-fibril-like protein.
As to the structure of AP protein, it is reported that the unit is formed as a pentagon by five subunits, the subunit having a molecular weight of 23,000 to 25,000, and the structure of AP protein is constructed by a pair of the unit making a parallel form.
It is confirmed that the AP protein is the same as SAP protein which is a normal serum protein by means of various methods. Accordingly, it is considered that AP protein is SAP protein deposited in tissue during circulation, that is, SAP protein is a precursor corresponding to AP protein. Although the function of AP protein in body and the relation of the protein with other amyloids are not clarified completely. However, there is a report that AP protein is an indispensable protein for an amyloid fibril. Accordingly, it is thought that the deposition of SAP protein is involved in the onset of amyloidosis.
Therapy for amyloidosis has been eagerly studied since, as described above, amyloidosis is a serious disease and its mortality is high. However, effective therapy especially drug therapy has not been found.
On the other hand, there has been tried a blood purification by extracorporeal circulation treatment, particularly plasmapheresis for treatment of amyloidosis.
Blood purification particularly plasmapheresis is the most effective therapy at present. However, the above blood purification has defects that it requires expensive and precious normal plasma or plasma preparations, that, in carrying out blood purification, useful components other than the precursors contained in a patient's plasma are removed at the same time, and the like. Therefore there is strongly desired a development of method for more selectively removing precursors such as SAA protein and SAP protein.
An object of the present invention is to solve the above problems and to provide a low-cost adsorbent for SA proteins, which can selectively remove SA proteins. Particularly, the object is to provide a low-cost SAA protein adsorbent which can selectively remove SAA proteins without removing HDL, and a low-cost SAP protein adsorbent which can selectively remove SAP proteins.